1. Field of the Invention
This invention relates to a composition and method for controlling appetite in humans. More particularly, the invention concerns the targeting of nutrients for the ileum to induce satiety in a human being.
2. Related Technology
A major class of weight control agents are drugs which act on the central nervous system (CNS) to suppress appetite. One major subclass of CNS appetite suppressant drugs interacts with cathecolaminergic receptors in the brainstem. These include controlled drugs such as amphetamine, phenmetrazine, and diethylproprion, and over-the-counter drugs such as phenylpropanolamine. Manizidol is another CNS active drug which, although not a catecholamine, activates the central nervous system. Each of these agents have potential for addiction and, at doses which effectively reduce appetite, i.e., suppress food intake by 20-30%, they induce significant CNS side effects, such as nervousness, loss of concentration, and insomnia. Another subclass of CNS active appetite control drugs interferes with serotonergic systems. D-fenfluramine, for example, releases and depletes brain serotonin, but it causes sedation at appetite suppressant levels, and it may precipitate depression upon its withdrawal. Fluoxetine is an inhibitor of serotonin re-uptake in the brainstem. However, at effective appetite control doses, Fluoxetine often causes nausea and asthenia, i.e., weakness, lassitude.
Another major class of weight control agents are drugs which promote malabsorption of nutrients through suppression of digestive enzymes. One agent in this category is Acarbose, a bacterial inhibitor of amylase and brushborder glycosidases. Another is tetrahydrolipostatin, a fungal inhibitor of lipases. These agents work by preventing digestion of carbohydrates and/or fats, thus creating an effective reduction in the number of calories absorbed, despite continued consumption. One drawback is that virtually complete inhibition of the respective enzymes must be maintained throughout the digestive period, a situation that can be rarely achieved. Thus, Acarbose was shown to be ineffective in humans, and tetrahydrolipostatin was shown to reduce human absorption of fat by only 30%. A second major drawback to this approach is that subjects taking these agents develop hyperphagia for other foodstuffs. For example, subjects taking tetrahydrolipostatin will consume more carbohydrate to compensate for the loss of fat absorption. Thus, the loss of calories from malabsorption is compensated by an increased intake of food, especially of foodstuffs of a different class.
A third class of weight control agents are noncaloric, non-nutritive dietary substitutes, like saccharin or Nutrasweet, sugar substitutes, and sucrose polyester, a fat substitute. These agents, while not absorbed, provide a taste and/or texture like the nutrient for which they are substituted. The disadvantage of these substitutes is that persons develop a hyperphagia to compensate for the reduction of calories by the substitution. With sucrose polyester, a nondigestible lipid, fat soluble, enterohepatically circulated vitamins partition into the unabsorbed polyester and are lost from the body, a potential problem which can also occur with tetrahydrolipostatin.
Thermogenic drugs are also sometimes used. The catecholamine drugs discussed above have some thermogenic activity, in addition to their suppression of appetite. Thyroid hormone is also commonly used.
Semi-starvation diets are universally effective in short term weight loss, but regain of weight after resumption of less restricted diets is the rule. Long term use of semi starvation diets is nutritionally unsound because of the development of multiple deficiencies of essential nutrients.
Surgical devices have also been employed to control appetite. Intragastric balloons have been placed endoscopically according to the theory that they increase the amount of gastric distension and thus augment satiety responses. However, they have been discontinued because, while they were not shown to be any better than restricted diets in promoting weight loss, their long term use was associated with severe side effects such as gastric ulceration and migration of the balloons into the small intestine resulting in intestinal obstructions.
Patients with morbid obesity (body mass index&gt;29 kg/m2, about 3% of the overweight population) are often encouraged to undergo bariatic surgery because, as a class, they suffer from more than four times the incidence of diabetes, cardiovascular disease, uterine and breast cancer, degenerative joint disease, and social stigmatization. Ileojejunal bypass, the first such surgery undertaken 30 years ago, has now been abandoned because of severe side effects such as poor subsequent malnutrition, fatal cirrhosis or renal failure. Biliopancreatic by-pass, gastric by-pass, and gastric partitioning (stapling) are the current procedures, but the long term side effects have not yet been determined.